title: Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers.
abstract: BACKGROUND
  Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies.
  
  
  METHODS
  A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated.
  
  
  RESULTS
  The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk.
  
  
  CONCLUSIONS
  Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers.
  
  
  CONCLUSIONS
  Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.
authors.affiliation: QueenslanInstitute for Medical Research, Brisbane, Australia.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Louise
authors.initials: L
authors.lastname: Marquart
authors.forename: Lesley
authors.initials: L
authors.lastname: McGuffog
authors.forename: Sue
authors.initials: S
authors.lastname: Healey
authors.forename: Olga
authors.initials: O
authors.lastname: Sinilnikova
authors.forename: Fei
authors.initials: F
authors.lastname: Wan
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beesley
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Anne-Catharine
authors.initials: AC
authors.lastname: Dressler
authors.forename: Daphne
authors.initials: D
authors.lastname: Gschwantler-Kaulich
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Jeff
authors.initials: J
authors.lastname: Weitzel
authors.forename: Henry
authors.initials: H
authors.lastname: Lynch
authors.forename: Judy
authors.initials: J
authors.lastname: Garber
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Margaret
authors.initials: M
authors.lastname: Cook
authors.forename: Clare T
authors.initials: CT
authors.lastname: Oliver
authors.forename: Debra
authors.initials: D
authors.lastname: Frost
authors.forename: Don
authors.initials: D
authors.lastname: Conroy
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Fiona
authors.initials: F
authors.lastname: Lalloo
authors.forename: Ros
authors.initials: R
authors.lastname: Eeles
authors.forename: Louise
authors.initials: L
authors.lastname: Izatt
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Davidson
authors.forename: Carol
authors.initials: C
authors.lastname: Chu
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Christina G
authors.initials: CG
authors.lastname: Selkirk
authors.forename: Mary
authors.initials: M
authors.lastname: Daly
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Muriel
authors.initials: M
authors.lastname: Belotti
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.forename: Laure
authors.initials: L
authors.lastname: Barjhoux
authors.forename: Carole
authors.initials: C
authors.lastname: Verny-Pierre
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Hélène
authors.initials: H
authors.lastname: Dreyfus
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Collonge-Rame
authors.forename: Matti A
authors.initials: MA
authors.lastname: Rookus
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef
authors.forename: Mieke
authors.initials: M
authors.lastname: Kriege
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Margreet G E M
authors.initials: MG
authors.lastname: Ausems
authors.forename: Theo A
authors.initials: TA
authors.lastname: van Os
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Hanne E J
authors.initials: HE
authors.lastname: Meijers-Heijboer
authors.forename: Marinus J
authors.initials: MJ
authors.lastname: Blok
authors.forename: Tuomas
authors.initials: T
authors.lastname: Heikkinen
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Francine
authors.initials: F
authors.lastname: Durocher
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Xianshu
authors.initials: X
authors.lastname: Wang
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.forename: Susan
authors.initials: S
authors.lastname: Domchek
authors.forename: Kate
authors.initials: K
authors.lastname: Nathanson
authors.forename: Ma
authors.initials: M
authors.lastname: Caligo
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
authors.forename: Annelie
authors.initials: A
authors.lastname: Liljegren
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Gail
authors.initials: G
authors.lastname: Tomlinson
authors.forename: Susan
authors.initials: S
authors.lastname: Neuhausen
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases